A method of performing a medical procedure, such as surgery, is provided. The system comprises a sensor to sense a biological characteristic, such as a chemical, physical or physiological characteristic of a bodily tissue or fluid. The method also comprises a nerve stimulator in communication with the...http://www.google.com/patents/US20050096707?utm_source=gb-gplus-sharePatent US20050096707 - Method and system for monitoring and controlling systemic and pulmonary circulation during a medical procedure

Method and system for monitoring and controlling systemic and pulmonary circulation during a medical procedureUS 20050096707 A1

Abstract

A method of performing a medical procedure, such as surgery, is provided. The system comprises a sensor to sense a biological characteristic, such as a chemical, physical or physiological characteristic of a bodily tissue or fluid. The method also comprises a nerve stimulator in communication with the sensor to inhibit beating of a heart when the sensor senses the biological characteristic at a first value; and a cardiac stimulator in communication with the sensor to stimulate beating of the heart when the sensor senses the biological characteristic at a second value.

Images(5)

Claims(60)

1-8. (canceled)

9. A method for controlling a heart beat during a medical procedure, comprising:

sensing a first gas level in a body;

stimulating a first nerve to inhibit beating of a heart;

performing at least one step of the medical procedure;

sensing a second gas level while performing the medical procedure;

stopping stimulation of the first nerve to allow beating of the heart when the second gas level is less than the initial gas level.

10. The method of claim 9 wherein the gas level is sensed for at least one of the characteristics selected from the group consisting of presence of oxygen, concentration of oxygen, presence of carbon dioxide, and concentration of carbon dioxide.

11. The method of claim 9 further comprising stimulating the heart with a cardiac stimulator to cause beating of the heart when the second gas level is less than the first gas level.

12. The method of claim 9 wherein the first gas level and second gas level are sensed in cerebral blood flow.

13. The method of claim 9 further comprising providing an alert signal when the second value is less than the first value.

14. The method of claim 12 wherein the alert signal is selected from the group consisting of: a visual signal, a flashing light, an audible signal, and a beeping tone.

15. The method of claim 9 wherein the medical procedure is started after sensing the first gas level, and wherein the second gas level is sensed during the medical procedure.

16. A method for performing a medical procedure, comprising:

sensing a characteristic of a bodily tissue or fluid via a sensor at a first value;

sending a first signal related to the sensed characteristic at a first value;

modifying the beating of a heart via a nerve stimulator in response to the first signal;

performing at least one step of the medical procedure;

sensing the characteristic via the sensor at a second value;

sending a second signal related to the sensed characteristic at a second value; and

modifying the beating of the heart via a cardiac stimulator in response to the second signal.

17. The method of claim 16 wherein modifying the beating of the heart via a nerve stimulator is performed automatically.

18. The method of claim 16 wherein modifying the beating of the heart via a nerve stimulator is performed manually.

19. The method of claim 16 wherein modifying the beating of the heart via a cardiac stimulator is performed automatically.

20. The method of claim 16 wherein modifying the beating of the heart via a cardiac stimulator is performed manually.

21. The method of claim 16 further comprising the delivery of a drug during the medical procedure.

22. The method of claim 21 wherein the drug is delivered via a drug delivery means.

23. The method of claim 22 wherein the drug delivery means is selected from the group consisting of a spray, a cream, an ointment, a medicament, a pill, a patch, a catheter, a cannula, a needle and syringe, a pump, and an iontophoretic drug delivery device.

24. The method of claim 21 wherein the drug is selected from the group consisting of a beta-blocker, a cholinergic agent, a cholinesterase inhibitor, a calcium channel blocker, a sodium channel blocker, a potassium channel agent, adenosine, an adenosine receptor agonist, an adenosine deaminase inhibitor, dipyridamole, a monoamine oxidase inhibitor, digoxin, digitalis, lignocaine, a bradykinin agent, a serotoninergic agonist, an antiarrythmic agent, a cardiac glycoside, a local anesthetic, atropine, a calcium solution, an agent that promotes heart rate, an agent that promotes heart contractions, dopamine, a catecholamine, an inotrope glucagon, a hormone, forskolin, epinephrine, norepinephrine, thyroid hormone, a phosphodiesterase inhibitor, prostacyclin, prostaglandin and a methylxanthine.

25. The method of claim 21 wherein the drug is naturally occurring or chemically synthesized.

26. The method of claim 16 wherein the nerve stimulator modifies the beating of the heart by stimulating a vagal nerve.

27. The method of claim 16 wherein the nerve stimulator modifies the beating of the heart by stimulating a carotid sinus nerve.

28. The method of claim 16 wherein the nerve stimulator modifies the beating of the heart by stimulating a fat pad.

29. The method of claim 16 wherein the bodily fluid is blood.

30. The method of claim 16 wherein the bodily tissue is cardiac tissue.

31. The method of claim 16 wherein the bodily tissue is a nerve.

32. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a chemical characteristic.

33. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a physical characteristic.

34. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a physiological characteristic.

35. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a fluid flow characteristic.

36. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a pressure characteristic.

37. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a temperature characteristic.

38. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is an electrical characteristic.

39. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a chemical concentration.

40. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a protein or peptide.

41. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a component of a metabolic process.

42. The method of claim 16 wherein the characteristic of a bodily tissue or fluid is a gas.

43. The method of claim 42 wherein the gas is oxygen.

44. The method of claim 42 wherein the gas is carbon dioxide.

45. The method of claim 16 wherein the sensor is selected from the group consisting of an imaging system, an electrical sensor, a chemical sensor, an electromagnetic interference sensor, an electrochemical sensor, a pressure sensor, a sound wave sensor, a magnetic sensor, an ultraviolet sensor, a visible light sensor, an infrared sensor, a radiation sensor, a flow sensor, a temperature sensor, a gas sensor, an optical sensor, a pH sensor, a potentiometric sensor, a fluorescence sensor and a biosensor.

46. The method of claim 16 wherein the nerve stimulator comprises one or more electrodes.

55. The method of claim 16 wherein the medical procedure is selected from the group consisting of a surgical procedure, a non-surgical procedure, a fluoroscopic procedure, a cardiac procedure, a vascular procedure, a neurosurgical procedure, an electrophysiology procedure, a diagnostic procedure, a therapeutic procedure, an ablation procedure, an endovascular procedure, a liver procedure, a spleen procedure, a pulmonary procedure, an aneurysm repair, an imaging procedure, a CAT scan procedure, a MRI procedure, a pharmacological therapy, a drug delivery procedure, a biological delivery procedure, a genetic therapy, a cellular therapy, a cancer therapy, a radiation therapy, a transplantation procedure, a coronary angioplasty procedure, a stent delivery procedure, an atherectomy procedure, a procedure that requires precise control of cardiac motion, a procedure that requires precise control of bleeding, a non-invasive procedure, a minimally invasive procedure, an invasive procedure, a port-access procedure, an endoscopic procedure, a sternotomy procedure, a thoracotomy procedure and a robotic procedure.

56. A method for performing a medical procedure, comprising:

sensing a first level of a biological characteristic in a body;

stimulating a nerve to inhibit beating of a heart;

performing at least one step of the medical procedure;

sensing a second level of the biological characteristic while performing the medical procedure;

stopping stimulation of the nerve to allow beating of the heart when the second level differs from the first level by a selective amount.

57. The method of claim 56 wherein the biological characteristic is a chemical characteristic.

58. The method of claim 56 wherein the biological characteristic is a physical characteristic.

59. The method of claim 56 wherein the biological characteristic is a physiological characteristic.

60. The method of claim 56 wherein the biological characteristic is a fluid flow characteristic.

61. The method of claim 56 wherein the biological characteristic is a pressure characteristic.

62. The method of claim 56 wherein the biological characteristic is a temperature characteristic.

63. The method of claim 56 wherein the biological characteristic is an electrical characteristic.

64. The method of claim 56 wherein the biological characteristic is a chemical concentration.

65. The method of claim 56 wherein the biological characteristic is a protein or peptide.

66. The method of claim 56 wherein the biological characteristic is a component of a metabolic process.

67. The method of claim 56 wherein the biological characteristic is a gas.

This invention relates to methods and systems for performing a medical procedure, especially procedures during which it is necessary to adjust the beating of the heart in order to allow the medical procedure to be performed on the heart or another organ. More particularly, this invention relates to methods and systems for monitoring and controlling one or more physiological and/or chemical parameters of a fluid such as blood or oxygen in the systemic and/or pulmonary circulatory systems during such a medical procedure.

BACKGROUND OF THE INVENTION

[0003]

The current leading cause of death in the United States is coronary artery disease in which the coronary arteries are blocked by atherosclerotic plaques or deposits of fat. The typical treatment to relieve a partially or fully blocked coronary artery is coronary artery bypass graph (CABG) surgery.

[0004]

CABG surgery, also known as “heart bypass” surgery, generally entails using a graph to bypass the coronary obstruction. The procedure is generally lengthy, traumatic and subject to patient risks. Among the risk factors involved is the use of a cardiopulmonary bypass (CPB) circuit, also known as a “heart-lung machine”, to pump blood and oxygenate the blood so that the patients heart may be stopped during the surgery.

[0005]

Conventional CABG procedures are typically conducted on a stopped heart while the patient is on a (CPB) circuit. A stopped heart and a CPB circuit enables a surgeon to work in a bloodless, still operative field. However, there a number of problems associated with CABG procedures performed while on CPB including the initiation of a systemic inflammatory response due to interactions of blood elements with the artificial material surfaces of the CPB circuit and global myocardial ischemia due to cardioplegic cardiac arrest. For these reasons, avoiding the use of CPB or cardioplegic cardiac arrest may help minimize post-operative complications.

[0006]

One method, as disclosed in U.S. Pat. No. 5,651,378 to Matheny and Taylor and in U.S. Pat. No. 5,913,876 to Taylor et al., for facilitating coronary bypass surgery on a beating heart and thereby avoid the use of CPB and cardioplegic cardiac arrest includes stimulating the vagal nerve electrically in order to temporarily stop or substantially reduce the beating of the heart. This may be followed by pacing the heart to start its beating.

[0007]

Another method, as disclosed in two published PCT applications, WO 99/09971 and WO 99/09973, both to Puskas, involves stopping the beating of the heart during coronary bypass surgery using electrical stimulation of the vagal nerve in combination with administration of drugs. Another method, as disclosed in U.S. Pat. No. 6,060,454 to Duhaylongsod, involves stopping the beating of the heart during coronary bypass surgery via the local delivery of drugs to the heart.

[0008]

Although it is desirable to stop the heart for a period of time in order to allow the surgeon to accomplish a required task without interference from heart movement, i.e. a motionless operative field, it is undesirable to have the heart stopped for too long a period of time since the body needs, among other things, constant supply of oxygen. In fact it is particularly important to maintain sufficient blood flow, and therefore oxygen flow, to the brain. A system for sensing biological parameters, such as the amount of blood flow or oxygen flow to the brain, could help determine whether these parameters are sufficient during a medical procedure.

[0009]

It would be desirable to provide a method for controllably stopping or slowing the heart intermittently in order to control blood flow in the systemic and/or pulmonary circulatory systems during a medical procedure.

[0010]

Additionally, it would be desirable to provide a means for monitoring one or more chemical, physical or physiological characteristics of a bodily tissue or fluid during the procedure.

[0011]

Additionally, it would be desirable to provide a method for controllably stopping or slowing the heart intermittently for diagnostic or therapeutic purposes.

[0012]

Additionally, it would, be desirable to provide a method for controllably stopping or slowing the heart intermittently in order to perform surgery on the heart or another organ.

SUMMARY OF THE INVENTION

[0013]

One aspect of the present invention provides a system for performing a medical procedure. The system includes a sensor to sense a biological characteristic, a nerve stimulator to inhibit beating of a heart when the sensor senses the biological characteristic at a first value and a cardiac stimulator to stimulate beating of the heart when the sensor senses the biological characteristic at a second value.

[0014]

The biological characteristic maybe a chemical characteristic of a tissue, a chemical characteristic of a fluid, a physical characteristic of a tissue, a physical characteristic of a fluid, a physiological characteristic of a tissue, and a physiological characteristic of a fluid. The biological characteristic may be a characteristic of a body component such as the blood, blood, cardiac tissue, or a nerve. The biological characteristic may be fluid flow, fluid pressure, mechanical pressure, temperature, electrical current, chemical concentration, presence of a protein, concentration of a protein, presence of a peptide, concentration of a peptide, a metabolic process, presence of a gas, concentration of a gas, presence of oxygen, concentration of oxygen, presence of carbon dioxide, concentration of carbon dioxide.

[0015]

The system may also include drug delivery means such as a spray, a cream, an ointment, a medicament, a pill, a patch, a catheter, a cannula, a needle and syringe, a pump, and an iontophoretic drug delivery device to deliver at least one drug during the procedure. The drug may be a beta-blocker, a cholinergic agent, a cholinesterase inhibitor, a calcium channel blocker, a sodium, channel blocker, a potassium channel agent, adenosine, an adenosine, receptor agonist, an adenosine deaminase inhibitor, dipyridamole, a monoamine oxidase inhibitor, digoxin, digitalis, lignocaine, a bradykinin agent, a serotoninergic agonist, an antiarrythmic agent, a cardiac glycoside, a local anesthetic, atropine, a calcium solution, an agent that promotes heart rate, an agent that promotes heart contractions, dopamine, a catecholamine, an inotrope glucagon, a hormoone, forskolin, epinephrine, norepinephrine, thyroid hormone, a phosphodiesterase inhibitor prostacyclin, prostagiandin and a methylxanthine. The drug may be naturally occurring or chemically syrithesized.

The sensor may be an imaging system, an electrical sensor, a chemical sensor, an electromagnetic interference sensor, an electrochemical sensor, a pressure sensor, a sound wave sensor, a magnetic sensor, an ultraviolet sensor, a visible light sensor, an infrared sensor, a radiation sensor, a flow sensor, a temperature sensor, a gas sensor, an optical sensor, a pH sensor, a potentiometric sensor, a fluorescence sensor and a biosensor.

The medical procedure may be a surgical procedure, a non-surgical procedures, a fluoroscopic procedure, a cardiac procedure, a vascular procedure, a neurosurgical procedure, an electrophysiological procedure, a diagnostic procedure, a therapeutic procedure, an ablation procedure, an endovascular procedure, a liver procedure, a spleen procedure, a pulmonary procedure, an aneurysm repair, an imaging procedure, a CAT scan procedure, a MRI procedure, a pharmacological therapy, a drug delivery procedure, a biological delivery procedure, a genetic therapy, a cellular therapy, a cancer therapy, a radiation therapy, a transplantation procedure, a coronary angioplasty procedure, a stent delivery procedure, an atherectomy procedure, a procedure that requires precise control of cardiac motion, a procedure that requires precise control of bleeding, a non-invasive procedure, a minimally invasive procedure, an invasive procedure, a port-access procedure, an endoscopic procedure, a sternotomy procedure, a thoracotomy procedure and a robotic procedure.

[0021]

Another aspect of the present invention provides a method for performing a medical procedure. A biological characteristic is sensed at a first value and a first signal related to the sensed biological characteristic is sent. Beating of a heart is inhibited in response to the first signal. The medical procedure is then performed. The biological characteristic is then sensed at a second value and a second signal related to the sensed biological characteristic at the second value is sent. Beating of the heart is stimulated in response to the second signal.

[0022]

Beating of the heart may be inhibited automatically in response to the first signal. Beating of the heart may be stimulated automatically in response to the second signal. At last one drug may be delivered during the medical procedure. A nerve may be stimulated to inhibit beating of the heart. Breathing may be stopped while beating of the heart is inhibited. Breathing may be stopped automatically.

[0023]

The biological characteristic may be a characteristic of blood, a characteristic of cardiac tissue, a characteristic of a nerve, a fluid flow characteristic, a pressure characteristic, a temperature characteristic, an electrical characteristic, a chemical concentration, a presence of a protein, a concentration of a protein, a presence of a peptide, a component of a metabolic process, a presence of a gas, a concentration of a gas, a presence of oxygen, a concentration of oxygen, a presence of carbon dioxide, a concentration of carbon dioxide, a chemical characteristic, a physical characteristic, and a physiological characteristic.

[0024]

Another aspect of the present invention provides a device for performing a medical procedure. The device includes a processor, a sensor to sense a biological characteristic and at least one nerve stimulation electrode. The processor receives a signal from the sensor and adjusts output from the nerve stimulation electrode in response to the signal.

[0025]

The sensor may be an imaging system, an electrical sensor, a chemical sensor, an electromagnetic interference sensor, an electrochemical sensor, a pressure sensor, a sound wave sensor, a magnetic sensor, an ultraviolet sensor, a visible light sensor, an infrared sensor, a radiation sensor, a flow sensor, a temperature sensor, a gas sensor, an optical sensor, a pH sensor, a potentiometric sensor, a fluorescence sensor and a biosensor.

The device may also include a drug pump for delivering at least one drug. The processor adjusts the output of the drug. The drug may be, for example, a beta-blocker, a cholinergic agent, a cholinesterase inhibitor, a calcium channel blocker, a sodium channel-blocker, a potassium channel agent, adenosine, an adenosine receptor agonist, an adenosine deamrinase inhibitor, dipyridamole, a monoamine oxidase inhibitor, digoxin, digitalis, lignocaine, a bradykinin agent, a serotoninergic agonist, an antiarrythmic agent, a cardiac glycoside, a local anesthetic, atropine, a calcium solution, an agent that promotes heart rate, an, agent that promotes heart contractions, dopamine, catecholamine, an inotrope glucagon, a hormone, forskolin, epinephrine norepinephrine, thyroid hormone, a phosphodiesterase inhibitor, prostacyclin, prostaglandin and a methylxanthine.

[0030]

The foregoing, and other, features and advantages of the invention will become further apparent from the following detailed description of the presently preferred embodiments, read in conjunction with the accompanying drawings. The detailed description and drawings are merely illustrative of the invention rather than limiting, the scope of the invention being defined by the appended claims in equivalence thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

[0031]

FIG. 1 is a schematic view of one embodiment of a system for monitoring at least one chemical, physical or physiological characteristic during a medical procedure in accordance with the present invention;

[0032]

FIG. 2 is a schematic view of one embodiment of a medical device in accordance with the present invention;

[0033]

FIG. 3 is a flow diagram of one embodiment of a method of performing a medical procedure in accordance with the present invention; and

[0034]

FIG. 4 is a timeline view of one embodiment of a system for monitoring at least one chemical, physical or physiological characteristic during a medical procedure in accordance with the present invention.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

[0035]

FIG. 1 shows a schematic view of one embodiment of a system for performing a medical procedure in accordance with the present invention at 100. System 100 comprises a sensor 5, a nerve stimulator 10, and a cardiac stimulator 20. System 100 may also feature a controller 30 and a breathing regulator 40.

[0036]

Sensor 5 may be any suitable blood gas sensor for measuring the concentration or saturation of a gas in the blood stream. For example, sensor 5 may be a sensor for measuring the concentration or saturation of oxygen or carbon dioxide in the blood. Alternatively, sensor 5 may be any suitable sensor for measuring blood pressure or flow, for example a Doppler ultrasound sensor system, or a sensor for measuring hematocrit (HCT) levels.

[0037]

Alternatively sensor 5 may be a biosensor, for example, comprising an Immobilized biocatalyst, enzyme, immunoglobulin, bacterial, mammalian or plant tissue, cell and/or subcellular fraction of a cell. For example, the tip of a biosensor may comprise a mitochondrial fraction of a cell, thereby providing the sensor with a specific biocatalytic activity.

[0038]

Sensor 5 may be based on potentiometric technology or fiber optic technology. For example, the sensor may comprise a potentiometric or fiber optic transducer. An optical sensor may be based on either an absorbance or fluorescence measurement and may include an UV, a visible or an IR light source.

[0039]

Sensor 5 may be used to detect naturally detectable properties representative of one or more characteristics, e.g., chemical, physical or physiological, of a patients bodily tissues or fluids. For example, naturally detectable properties of patients bodily tissues or fluids may include pH, fluid, flow, electrical current, temperature pressure, components of metabolic processes, chemical concentrations, for example, the absence or presence of specific peptides, proteins, enzymes, gases, ions, etc.

In one embodiment of the invention, sensor 5 may be a cerebral blood flow sensor, in which case, the sensor may be placed in any suitable manner for sensing cerebral blood flow. For example, sensor 5 may be inserted between the skull and the dura of the brain. Alternatively, sensor 5 may be placed in the patients neck. For example, at least a portion of sensor 5 may be placed in an artery, such as the carotid artery. Such a placement would allow measurement of blood as it flows to the brain. Alternatively, sensor 5 may be placed in a vein, such as the jugular vein. This placement would allow measurement of blood as it flows from the brain.

[0042]

In the case of blood oxygen saturation sensing, a certain level of oxygen generally remains in the blood as it flows from the brain. This level may be established by measuring the patients oxygen prior to surgery. If blood measured by sensor 5 in the vein has oxygen below the established level, the brain is consuming all or most of the oxygen flowing to it and probably requires additional oxygen. Other suitable placements of sensor 5 may be possible. Sensor 5 may be used to alert a surgeon to changes in the patients circulatory, system.

[0043]

System 100 may also include a nerve stimulator 10. In one embodiment, the nerve stimulator 10 may be used to electrically manipulate cardiac rhythm by stimulating the vagus nerve. This vagal stimulation may produce asystole (slowing or stopping of the hearts beating.) Once this induced asystole is stopped, i.e. once the vagal stimulation is stopped, the heart may be allowed to return to its usual cardiac rhythm. Alternatively, the heart may be paced with an electrical pacing system, thereby maintaining a normal cardiaic output. Vagal stimulation, alone or in combination with electrical pacing, may be used selectively and intermittently to allow a surgeon to perform a medical procedure during intermittent periods of asystole.

[0044]

It is known that stimulation of the vagus nerve can reduce the sinus rate, as well as prolong AV conduction time or if stimulation energies are high enough, induce AV node block. Use of vagal nerve stimulation to treat supraventricular arrhythmias and angina pectoris is disclosed in the article “Vagal Tuning” by Bilgutay et al., Journal of Thoracic and Cardiovascular Surgery, Vol. 56, No. 1, July, 1968, pp. 71-82. It is also known that stimulation of the carotid sinus nerve produces a similar result, as disclosed in the article “Carotid Sinus Nerve Stimulation in the Treatment of Angina. Pectoris and Supraventricular Tachycardia” by Braunwald et al., published in California Medicine, Vol. 112, pp. 41-50, March, 1970.

[0045]

As set forth in “Functional Anatomy of the Cardiac Efferent Innervation” by Randall et al., in Neurocardiology, edited by Kulbertus et al, Futura Publishing Co., 1988, direct surgical excision of the fat pad associated with the SA node affects the functioning of the SA node without Significantly affecting the AV node. Similarly, excision of the fat pad associated with the AV node affects functioning of the AV node without significantly affecting the SA node.

[0046]

As set forth in the article “Parasympathetic Postganglionic Pathways to the Sinoatrial Node”, Bluemel et al., Am. J. Physiol. 259, (Heart Circ. Physiol. 28). H1504-H1511, 1990, stimulation of the fat pad associated with the SA node results in slowing of the sinus rate without the accompanying prolongation of AV conduction time which normally results from vagal nerve stimulation. The article also indicates that stimulation of the fat pad associated with the AV node is believed to produce corresponding effects limited to the AV node, i.e., extension of the AV conduction time without concurrent slowing of the sinus rate.

[0047]

As set forth in the article “Neural Effects on Sinus Rate and Atrial Ventricular Conduction Produced by Electrical Stimulation From a Transvenous Electrode Catheter in the Canine Right Pulmonary Artery” by Cooper et al., published in Circulation Research, Vol. 46, No. 1, January, 1980, pp. 48-57, the fat pads associated with both the AV node and the SA node may be stimulated by means of electrodes located in the right pulmonary artery. The results obtained include-both a depression of the sinus rate and a prolongation of the AV conduction time in response to continuous stimulation at 2-80 Hz at up to 50 ma.

[0048]

Generally in healthy individuals, the SA node functions as the pacemaker. Normal heart rhythm associated with the SA node is typically referred to as sinus rhythm. When the SA node fails, the AV node generally takes over creating a heart rate of approximately 35 to 60 beats per minute. Heart rhythm associated with the AV node is typically referred to as nodal rhythm. When the AV node itself is blocked or injured, a new seven slower pacemaker site may form at the junction of the AV node and the His bundle. Heart rhythm associated with this junction is typically referred to as junctional, escape rhythm. When this junction site is inhibited, the Purkinje fibers in the His bundle or below may act as a pacemaker creating a heart rate of approximately 30 beats per minute. Heart rhythm associated with the Purkinje fibers is typically referred to as idioventricular rhythm.

[0049]

In one embodiment of the present invention, nerve stimulator 10 may be used to electrically manipulate cardiac rhythm by stimulating the carotid sinus nerve, the fat pad associated with the SA node, the fat pad associated with the AV node, the junction of the AV node and the His bundle and/or the Purkinje fibers.

[0050]

In one embodiment of the present invention, nerve stimulator 10 is used alone or in combination with other heart rate inhibiting agents to temporarily stop or slow the beating heart, thereby eliminating or reducing heart motion and/or blood flow during a medical procedure. For example, the present invention may be used to eliminate or reduce motion in the anastomosis field during CABG Procedures such that a facilitated anastomosis procedure may be performed; safely and effectively. The number of occasions that the vagal nerve may be stimulated depends on the type of medical procedure to be performed. Likewise, the type of medical procedure to be performed will dictate the duration of the individual electrical stimulations.

[0051]

Nerve stimulator 10 may be powered by AC current, DC current or it may be battery powered either by a disposable or rechargeable battery. Nerve stimulator 10 may be configured to synchronize activation and deactivation of breathing regulator 40 with vagal stimulation, thereby minimizing or eliminating unwanted heart and chest motion associated with the patients breathing. Nerve stimulator 10 may comprise a surgeon controlled switch box. A switch may be incorporated in or on one of the surgeons instruments, such as surgical site retractor, or any other location easily and quickly accessed by the surgeon for regulation of the nerve stimulator by the surgeon. The switch may be, for example, a hand switch, a footswitch, or a voice-activated switch comprising voice-recognition technologies.

[0052]

A visual and/or audible signal used to alert a surgeon to the completion or resumption of vagal nerve stimulation may be incorporated into nerve stimulator 10. For example, a beeping tone or flashing light that increases in frequency as the nerve stimulation period should end or begin may be used.

[0053]

Nerve stimulator 10 may be slaved to cardiac stimulator 20 or cardiac stimulator 20 may be slaved to nerve-stimulator 10. For example, the output of cardiac stimulator 20 may be off whenever the output of nerve stimulator 10 is on. Software controlling cardiac stimulator 20 may be designed to automatically commence cardiac pacing if the heart does not resume beating within a pre-determined interval after cessation of vagal nerve stimulation. In addition, the software controlling nerve stimulator 10 may be designed to automatically stop vagal nerve stimulation if the heart has been stopped for to long. For example, a predetermined time interval may be set to automatically stop vagal stimulation. In one embodiment of the invention, if sensor 5 of the present invention indicates that not enough blood is flowing to the brain, vagal stimulation may be stopped, thereby allowing the heart to beat again.

[0054]

In another embodiment it may be necessary to use cardiac stimulator 20 to actively stimulate the heart into beating again. For example in one embodiment of the present invention, sensor 5 may indicate that not enough, blood is flowing to the brain causing nerve stimulator 10 to be automatically turned off and cardiac stimulator 20 to be automatically turned on. Alternatively, the surgeon may turn on cardiac stimulator 20 to begin stimulation.

[0055]

Just like nerve stimulator 10, cardiac stimulator 20 may be intermittently stopped and, started to allows the surgeon to perform individual steps of a medical procedure.

[0056]

Cardiac stimulator 20 may be a conventional ventricular demand pacer or dual chamber (atrial-ventricular) pacer. Cardiac stimulator 20 may be powered by AC current, DC current or it may be battery powered either by a disposable or re-chargeable battery. Cardiac stimulator 20 may be configured to synchronize activation and deactivation of breathing regulator 40 with pacing, thereby minimizing or eliminating unwanted heart and chest motion associated with the patients breathing.

[0057]

Cardiac stimulator 20 may be any conventional pacing device suitable for ventricular demand pacing and having leads electrically coupled to a switch box. Cardiac stimulator 20 may be combined in a single unit with a switch box. A switch may be incorporated in or on one of the surgeon's instruments, such as surgical site retractor, or any other location easily and quickly accessed by the surgeon for regulation of the cardiac stimulator by the surgeon. The switch may be, for example, a hand switch, a foot-switch, or a voice-activated switch comprising voice-recognition technologies. A single switch may be used to regulate both cardiac stimulator 20 and nerve stimulator 10.

[0058]

A visual and/or audible signal used to prepare a surgeon for the resumption of pacing may be incorporated into cardiac stimulator 20. For example, a beeping tone or flashing light that increases in frequency as the pacing period ends may be used. A single signaling method or device may be used for both cardiac stimulator 20 and nerve stimulator 10.

[0059]

Sensor 5, nerve stimulator 10 and/or cardiac stimulator 20 may be slaved to a robotic system or a robotic system may be slaved to sensor 5, nerve stimulator 10 and/or cardiac stimulator 20. Breathing regulator 40 and other components may also be slaved to such a system. Computer and voice-controlled robotic systems that position and maneuver endoscopes and/or other surgical instruments for performing microsurgical procedures such as anastomoses through small incisions may be used by a surgeon to perform precise and delicate maneuvers. These robotic systems may allow a surgeon to perform a variety of microsurgical procedures-including endoscopic CABG. Endoscopic CABG may allow multiple occluded coronary arteries to be bypassed without a thoracotomy or mini-thoracotomy. Heart valve repair and replacement may also be other surgical applications for these robotic systems. In general, robotic systems may include head-mounted displays, which integrate 3-D visualization of surgical anatomy and related diagnostic and monitoring data, miniature high resolution 2-D and 3-D digital cameras, a computer, a high power light source and a standard video monitor.

[0060]

System 100 may also include a breathing regulator 40. In one embodiment, the breathing regulator 40 may be used to stimulate the phrenic nerve in order to provide a diaphragmatic pacemaker. Breathing regulator 40 may comprise one or more electrodes for supplying electrical current to the phrenic nerve to control breathing during vagal and/or cardiac stimulation and/or destimulation. Electrodes used to stimulate the phrenic nerve may be, for example, non-invasive, e.g., clips, or invasive, e.g., needles or probes. The application of an electrical stimulus to the phrenic nerve may include, but is not limited to bipolar and/or monopolar techniques. Different electrode positions are accessible through various access openings, for example, in the cervical or thorax regions. Nerve stimulation electrodes may be positioned through a thoracotomy, sternotomy, endoscopically through a percutaneous port, through a stab wound or puncture, through a small incision, placed on the skin or in combinations thereof. The present invention may include various electrodes, catheters and electrode catheters suitable for phrenic nerve stimulation to control breathing.

[0061]

Phrenic nerve stimulation electrodes may be intravascular, patch-type, balloon-type, basket-type, umbrella-type, tape-type, cuff-type, suction-type, screwy-type, barb-type, bipolar, monopolar, metal, wire, endotracheal, endoesophageal intravascular, transcutaneous or intracutaneous electrodes. Guided or steerable catheter devices comprising electrodes may be used alone- or in combination with the nerve stimulation electrodes. For example, a catheter comprising one or more wire, metal strips or metal foil electrodes or electrode arrays may be used. The catheter may comprise, for example, a balloon, which may be inflated with air or liquid to press the electrodes firmly against a vessel wall that lays adjacent the phrenic nerve.

[0062]

Phrenic nerve stimulation electrodes may be oriented in any fashion along the catheter device, including longitudinally or transversely. Various techniques such as ultrasound, fluoroscopy and echocardiography may be used to facilitate positioning of the electrodes. If desired or necessary, avoidance of obstruction of blood flow may be achieved with notched catheter designs or with catheters which incorporate one or more tunnels or passageways.

[0063]

In another embodiment, breathing regulator 40 may comprise a connector, which interfaces with a patients respirator, and sends a logic signal to activate or deactivate the respirator to control breathing during vagal and/or cardiac stimulation and/or destimulation.

[0064]

FIG. 2 shows one embodiment of the present invention at 200. In this embodiment, the elements named above may be combined or connected to a control unit along with other components. Unit 200 may be used to coordinate the various elements.

[0065]

Unit 200 may incorporate a controller as described above or any suitable processor 230. For example, the processor may process sensed blood information from sensor 205. The controller may store and/or process such information before, during and/or after a medical procedure. For example, the patients oxygen concentration or blood pressure may be sensed, stored and processed prior to and during surgery.

[0066]

Unit 200 may also incorporate a nerve stimulator. For example, FIG. 2 shows an electrode for nerve stimulation at 210. Electrodes used to stimulate a nerve such as the vagal nerve may be, for example, non-invasive, e.g., clips, or invasive, e.g., needles or probes. The application of an electrical stimulus to the right or left vagal nerve may include, but is not limited to bipolar and/or monopolar techniques. Different electrode positions are accessible through various access openings, for example, in the cervical or thorax regions. Nerve stimulation electrodes 210 may be positioned through a thoracotomy, sternotomy, endoscopically through a percutaneous port, through a stab wound or puncture, through a small incision in the neck or chest, through the internal jugular vein, the esophagus, the trachea, placed on the skin or in combinations thereof. Electrical stimulation may be carried out on the right vagal nerve, the left vagal nerve or to both nerves simultaneously or sequentially. The present invention may include various electrodes, catheters and electrode catheters suitable for vagal nerve stimulation to temporarily stop or slow the beating heart alone or in combination with other heart rate inhibiting agents.

[0067]

Nerve stimulation electrodes 210 may be endotracheal, endoesophageal, intravascular, transcutaneous, intracutaneous, patch-type, balloon-type, cuff-type; basket-type, umbrella-type, tape-type, screw-type, barb-type, metal, wire, or suction-type electrodes. Guided or steerable catheter devices comprising electrodes may be used alone or in combination with the nerve stimulation electrodes 210. For example, a catheter comprising one or more wire, metal strips or metal foil electrodes or electrode arrays maybe inserted into the internal jugular vein to make electrical contact with the wall of the internal jugular vein, and thus stimulate the vagal nerve adjacent to the internal jugular vein. Access to the internal jugular vein may be via, for example, the right atrium, the right atrial appendage, the inferior vena cava or the superior vena cava. The catheter may comprise, for example, a balloon, which may be inflated with air or liquid to press the electrodes firmly against the vessel wall. Similar techniques may be performed by insertion of a catheter type device into the trachea or esophagus. Additionally tracheal tubes and esophageal tubes comprising electrodes may be used.

[0068]

Nerve stimulation electrodes 210 may be oriented in any fashion along the catheter device, including longitudinally or transversely. Various techniques such as ultrasound, fluoroscopy and echocardiography may be used to facilitate positioning of the electrodes. If desired or necessary, avoidance of obstruction of blood flow may be achieved with notched catheter designs or with catheters which incorporate one or more tunnels or passageways.

[0069]

In one embodiment of the present invention the location of the electrodes 210 is chosen to elicit maximum bradycardia effectiveness while minimizing current spread to adjacent tissues and vessels and to prevent the induction of post stimulation tachycardia. Furthermore, a non-conductive material such as configurations to shield them from the surrounding tissues and vessels, while exposing their confronting edges and surfaces for positive contact with the vagal nerve or selected tissues.

[0070]

Unit 200 may also incorporate a cardiac stimulator. For example, FIG. 2 shows a electrode for stimulation of the heart at 220. Cardiac electrodes 220 used to stimulate the heart may be, for example, non-invasive, e.g., clips, or invasive, e.g. needles or probes. Electrodes 220 may be positioned through a thoracotomy, sternotomy, endoscopically through a peutaneous port, through a stab wound or puncture, through a small incision in the chest, placed on the chest or in combinations thereof. The present invention may also use various electrodes, catheters and electrode catheters and to pacing the heart, e.g., epicardial, patch-type, intravascular, balloon-type, basket-type, umbrella-type tape-type electrodes, suction-type, pacing electrodes, endotracheal electrodes, endoesophageal electrodes, transcutaneous electrodes, intracutaneous electrodes, screw-type electrodes, barb-type electrodes, bipolar electrodes, monopolar electrodes, metal electrodes, wire electrodes and cuff electrodes, Guided or steerable catheter devices comprising electrodes may be used alone or in combination with the electrodes. Controller 230 may be used to gather information from nerve stimulation electrodes 210 and cardiac stimulation electrodes 220. Controller 230 may also be used to control the stimulation levels and stimulation duration from nerve stimulation electrodes 210 and cardiac stimulation electrodes 220. Controller 230 may also gather and process information from sensor 205. This information may be used to adjust-stimulation levels and stimulation times from nerve stimulation electrodes 210 and cardiac stimulation electrodes 220.

[0071]

Unit 200 may incorporate one or more switches to facilitate regulation of the various components by the surgeon. One example of such a switch is shown as foot pedal 250. The switch may also be, for example, a hand switch, or a voice-activated switch comprising voice-recognition technologies. The switch may be incorporated in or on one of the surgeons instruments, such as surgical site retractor, or any other location easily and quickly accessed by the surgeon. Unit 200 may also include a display 260. Unit 200 may also include other means of indicating the status of various components to the surgeon such as a numerical display, gauges, a monitor display or audio feedback. Unit 200 may also include one or more visual and/or audible signals used to prepare a surgeon for the start or stop of nerve stimulation and/or cardiac stimulation.

[0072]

FIG. 3 shows a flow diagram of one embodiment of the present invention. The patient is prepared for a medical procedure at 500. Once the patient is prepared, the initial state of cerebral blood circulation is measured (Block 505). Such measurements may include for example blood flow, oxygen concentration, carbon dioxide concentration, etc. The initial state of cerebral blood circulation is then used as a gauge to compare with the state of cerebral blood circulation during the procedure.

[0073]

At Block 510, a nerve that controls the beating of the heart is stimulated. Such a nerve may be for example a vagal nerve. At Block 510, one or more of a variety of pharmacological agents or drugs may be delivered. These drugs may produce reversible asystole of a heart while maintaining the ability of the heart to be electrically paced.

[0074]

A variety of pharmacological agents or drugs may also be delivered at other times during the procedure 500. These drugs may also produce reversible asystole of a heart while maintaining the ability of the heart to be electrically paced. Other drugs may be administered for a variety of functions and purposes as described below. Drugs may be delivered at any appropriate time during the medical procedure, for example, at the beginning of the procedure, intermittently during the procedure, continuously during the procedure or following the procedure.

[0075]

Drugs, drug formulations or compositions suitable for administration to a patient during a medical procedure may include a pharmaceutically acceptable carrier or solution in an appropriate dosage. There are a number of pharmaceutically acceptable carriers that may be used for delivery of various drugs, for example, via direct injection, oral delivery suppository delivery, transdermal delivery, epicardial delivery and/or inhalation delivery. Pharmaceutically acceptable carriers include a number of solutions, preferably sterile, for example, water, saline. Ringers solution and/or sugar solutions such as dextrose in water or saline. Other possible carriers that may be used include sodium citrate, citric acid, amino acids, lactate, mannitol, maltose, glycerol, sucrose, ammonium chloride, sodium chloride, potassium chloride, calcium chloride, sodium lactate, and/or sodium bicarbonate. Carrier solutions may or may not be buffered.

[0076]

Drug formulations or compositions may include antioxidants or preservatives such as ascorbic acid. They may also be in a pharmaceutically acceptable form for parenteral administration, for example to the cardiovascular system, or directly to the heart, such as intracoronary infusion or injection. Drug formulations or compositions may comprise agents that provide a synergistic effect when administered together. A synergistic effect between two or more drugs or agents may reduce the amount that normally is required for therapeutic delivery of an individual drug or agent. Two or more drugs may be administered, for example, sequentially or simultaneously. Drugs may be administered via one or more bolus injections and/or infusions or combinations thereof. The injections and/or infusions may be continuous or intermittent. Drugs may be administered, for example, systemically or locally, for example, to the heart, to a coronary artery and/or vein, to a pulmonary artery and/or vein, to the right atrium and/or ventricle, to the left atrium and/or ventricle to the aorta, to the AV node, to the SA node, to a nerve and/or to the coronary sinus. Drugs may be administered or delivered via intravenous, intracoronary and/or intraventricular administration in a suitable carrier. Examples of arteries that may be used to deliver drugs to the AV node include the AV node artery, the right coronary artery, the right descending coronary artery, the left coronary artery, the let anterior descending coronary artery and Kugel's artery. Drugs may be delivered systemically, for example, via oral, transdermal, intranasal suppository or inhalation methods. Drugs also may be delivered via a pill, a spray, a cream, an ointment or a medicament formulation.

[0077]

Drugs may be delivered via a drug delivery device that may comprise a catheter, such as a drug delivery catheter or a guide catheter, a patch, such as a transepicardial patch that slowly releases drugs directly into the myocardium, a cannula, a pump and/or a hypodermic needle and syringe assembly. A drug delivery catheter may include an expandable member, e.g., a low-pressure balloon, and a shaft having a distal portion, wherein the expandable member is disposed along the distal portion. A catheter for drug delivery may comprise one or more lumens and may be delivered endovascularly via insertion into a blood vessel, e.g., an artery such as a femoral, radial, subclavian or coronary artery. The catheter can be guided into a desired position using various guidance techniques, e.g., flouroscopic guidance and/or a guiding catheter or guide wire techniques. Drugs may be delivered via an iontophoretic drug delivery device placed on the heart. In general, the delivery of ionized drugs may be enhanced via a small current applied across two electrodes. Positive ions may be introduced into the tissues from the positive pole, or negative ions from the negative pole. The use of iontophoresis may markedly facilitate the transport of certain ionized drug molecules. For example, lidocaine hydrochloride may be applied to the heart via a drug patch comprising the drug. A positive electrode could be placed over the patch and current passed. The negative electrode would contact the heart or other body part at some desired distance point to complete the circuit. One or more of the electrodes may also be used as nerve stimulation electrodes 210 or as cardiac stimulation electrodes 220.

[0078]

The two divisions of the autonomic nervous system that regulate the heart have opposite functions. First, the adrenergic or sympathetic nervous system increases heart rate by releasing epinephrine and norepinephrine. Second, the parasympathetic system also known as the cholinergic nervous system or the vagal nervous system decreases heart rate by releasing acetylcholine. Catecholamines such as norepinephrine (also called noradrenaline) and epinephrine (also called adrenaline) are agonists for beta-adrenergic receptors. An agonist is a stimulant biomolecule or agent that binds to a receptor.

[0079]

Beta-adrenergic receptor blocking agents compete with beta-adrenergic receptor stimulating agents for available beta-receptor sites. When access to beta-receptor sites are blocked by receptor blocking agents, also known as beta-adrenergic blockade, the chronotropic or heart rate, inotropic or contractility, and vasodilator responses to receptor stimulating agents are decreased proportionately. Therefore, beta-adrenergic receptor blocking agents are agents that are capable of blocking beta-adrenergic receptor sites.

[0080]

Since beta-adrenergic receptors are concerned with contractility and heart rate, stimulation of beta-adrenergic receptors, in general, increases heart rate, the contractility of the heart and the rate of conductor of electrical impulses through the AV node and the conduction system.

[0081]

Drugs, drug formulations and/or drug compositions that may be used according to this invention may include any naturally occurring or chemically synthesized (synthetic analogues) beta-adrenergic receptor blocking agents. Beta-adrenergic receptor or □-adrenegic blocking agents are also known as beta-blockers or □-blockers and as class II antiarrhythmics.

[0082]

The term “beta-blocker” appearing herein may refer to one or more agents that antagonize the effects of beta-stimulating catecholamines by blocking the catecholamines ines from binding to the beta-receptors. Examples of beta-blockers include, but are not limited to a acebutolol, alprenolol, atenolol, betantolol, betaxolol, becantolol, bisoprolol, carterolol, celiprblol, chlorthalidone, esmolol, labetalol, metoprolol, nadolol, penbutolol, pindolol, propranolol, oxprenolol, sotalol, teratolo, timolol and combinations, mixtures and salts thereof.

[0083]

The effects of administered beta-blockers may be reversed by administration of beta-receptor agonists, e.g., dobutamine or isoproterenol.

[0084]

The parasympathetic or cholinergic system participates in control of heart rate via the sinoatrial (SA) node, where it reduces heart rate. Other cholinergic effects include inhibition of the AV node and an inhibitory effect on contractile force. The cholinergic system acts through the vagal nerve to release acetylcholine, which, in turn, stimulates cholinergic receptors. Cholinergic receptors are also known as muscarinic receptors. Stimulation of the cholinergic receptors decreases the formation of CAMP. Stimulation of cholinergic receptors generally has an opposite effect on heart rate compared to stimulation of beta-adrenergic receptors. For example, beta-adrenergic stimulation increases heart rate, whereas cholinergic stimulation decreases it. When vagal tone is high and adrenergic tone is low, there is a marked slowing, of the heart (sinus bradycardia). Acetylcholine effectively reduces the amplitude, rate of increase and duration of the SA node action potential. During vagal nerve stimulation, the SA node does not arrest. Rather, pacemaker function may shift to cells that fire at a slower rate. In addition, acetylcholine may help open certain potassium channels thereby creating an outward flow of potassium ions and hyperpolarization. Acetylcholine also slows conduction through the AV node.

[0085]

Drugs, drug formulations and/or drug compositions that may be used according to this invention may include any naturally occurring or chemically synthesized (synthetic analogues) cholinergic agent. The term “cholinergic agent” appearing herein may refer to one or more cholinergic receptor modulators, or agonists. Examples of cholinergic agents include, but are not limited to, acetylcholine, carbachol (carbamyl choline chloride), bethanechol, methacholine, arecoline, norarecoline and combinations, mixtures and/or salts thereof.

[0086]

Drugs, drug formulations and/or drug compositons that may be used according to this invention may include any naturally occurring or chemically synthesized cholinesterase inhibitor. The term “cholinesterase inhibitor” appearing herein may refer to one or more agents that prolong the action of acetylcholine by inhibiting its destruction or hydrolysis by cholinesterase. Cholinesterase inhibitors are also known as acetylcholinesterase inhibitors. Examples of cholinesterase inhibitors include, but are not limited to, edrophonium, neostigmine, neostigmine methylsulfate; pyridostigmine, tacrine and combinations, mixtures and/or salts thereof.

[0087]

There are ion-selective channels within certain cell membranes. These ion selective channels include calcium channels, sodium channels and/or potassium channels. Therefore, other drugs, drug formulations and/or drug compositions that may be used according to this invention may include any naturally occurring or chemically synthesized calcium channel blocker. Calcium channel blockers inhibit the inward flux of calcium ions across cell membranes of arterial smooth muscle cells and myocardial cells. Therefore, the term “calcium channel blocker” appearing herein may refer to one or more agents that inhibit or block the flow of calcium ions across a cell membrane. The calcium channel is generally concerned with the triggering of the contractile cycle. Calcium channel, blockers are also known as calcium ion influx inhibitors, slow channel blockers, calcium ion antagonists, calcium channel antagonist drugs and as class IV antiarrhythmics. A commonly used calcium channel blocker is verapamil.

[0088]

Administration of a calcium channel blocker, e.g., verapamil, generally prolongs the effective refractory period within the AV node and slows AV conduction in a rate-related manner, since the electrical activity through the AV node depends significantly upon the influx of calcium ions through the slow channel. A calcium channel blocker has the ability to slow a patients heart rate, as well as produce AV block. Examples of calcium channel blockers include, but are not limited to, amiloride, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nicardipine, nifedipine (dihydropyridines), nickel, nimodinpine, nisoldipine, nitric oxide (NO), norverapamil and veraparhil and combinations, mixtures and/or salts thereof. Verapamil and diltiazem are very effective at inhibiting the AV node, whereas drugs of the nifedipine family have a lesser inhibitory effect on the AV node. Nitric oxide (NO) indirectly promotes calcium channel closure. NO may be used to inhibit contraction. NO may also be used to inhibit sympathetic outflow, lessen the release of norepinephrine, cause vasodilation, decrease heart rate and decrease contractility. In the SA node, cholinergic stimulation leads to formation of NO.

[0089]

Other drugs, drug formulations and/or drug compositions that may be used according to this invention may include any naturally occurring or chemically synthesized sodium channel blocker. Sodium channel blockers are also known as sodium channel inhibitors, sodium channel blocking agents, rapid channel blockers or rapid channel inhibitors. Antiarrhythmic agents that inhibit or block the sodium channel are known as class I antiarrhythmics, examples include, but are not limited to, quinidine and quinidine-like agents, lidocaine and lidocaine-like agents, tetrodotoxin, encainide, flecainid and combinatons, mixtures and/or salts thereof. Therefore, the term “sodium channel blocker” appearing herein may refer to one or more agents that inhibit or block the flow of sodium ions across a cell membrane or remove the potential difference across a cell membrane. For example, the sodium channel may also be totally inhibited by increasing the extracellular potassium levels to depolarizing hyperkalemic values, which remove the potential difference across the cell membrane. The result is inhibition of cardiac contraction with cardiac arrest (cardioplegia). The opening of the sodium-channel (influx of sodium) is for swift conduction of the electrical impulse throughout the heart.

[0090]

Other drugs, drug formulations and/or drug compositions that may be used according to this invention may include any naturally occurring or chemically synthesized potassium channel agent. The term “potassium channel agent” appearing herein may refer to one or more agents that impact the flow of potassium ions across the cell membrane. There are two major types of potassium channels. The first type of channel is voltage-gated and the second type is ligand-gated. Acetylcholine-activated potassium channels, which are ligand-gated channels, open in response to vagal stimulation and the release of acetylcholine. Opening of the potassium channel causes hyperpolarization, which decreases the rate at which the activation threshold is reached. Adenosine is one example of a potassium channel opener. Adenosine slows conduction through the AV node. Adenosine, a breakdown product of adenosine triphosphate inhibits the AV node and atria. In, atrial tissue, adenosine causes the shortening of the action potential duration and causes hyperpolarization. In the AV node, adenosine has similar effects and also decreases the action potential amplitude and the rate of increase of the action potential. Adenosine is also a direct vasodilator by its actions on the adenosine receptor on vascular smooth muscle cells. In addition, adenosine acts as a negative neuromodulator, thereby inhibiting release of norepinephrine. Class III antiarrhythmic agents also known as potassium channel inhibitors lengthen the action potential duration and refractoriness by blocking the outward potassium channel to prolong the action potential. Amiodarone and d-sotalol are both examples of class III antiarrhythmic agents.

[0091]

Potassium is the most common component in cardioplegic solutions. High extracellular potassium levels reduce the membrane resting potential. Opening of the sodium channel, which normally allows rapid sodium influx during the upstroke of the action potential, is therefore inactivated because of a reduction in the membrane resting potential. The present invention may be combined with conventional CPB, the induced asystole as described by this invention may serve as a substitute for conventional cardioplegic arrest. For example, the combination of drugs and vagal stimulation may be used as a cardioplegic agent in a variety of medical procedures.

[0092]

Drugs, drug formulations and/or drug compositions that may be used during according to this invention may comprise one or more of any naturally occurring or chemically synthesized beta-blocker, cholinergic agent, cholinesterase inhibitor, calcium channel blocker, sodium channel blocker, potassium channel agent, adenosine, adenosine receptor agonist, adenosine deaminase inhibitor, dipyridamole, monoamine oxidase inhibitor, digoxin, digitalis, lignocaine, bradykinin agents, serotoninergic agonist, antiarrythmic agents, cardiac glycosides, local anesthetics and combinations or mixtures thereof. Digitalis and digoxin both inhibit the sodium pump. Digitalis is a natural inotrope derived from plant material, while digoxin is a synthesized inotrope. Dipyridamole inhibits adenosine deaminase, which breaks down adenosine. Drugs, drug formulations and/or drug compositions capable of reversibly suppressing autonomous electrical conduction at the SA and/or AV node, while still allowing the heart to be electrically paced to maintain cardiac output may be used according to this invention.

[0093]

In one embodiment, thee cardiac asystole produced in accordance with the resent invention is reversible e.g., chemically such as by the administration of atropine or by natural forces. Beta-adrenergic stimulation or administration of calcium solutions may be used to reverse the effects of a calcium channel blocker such as verapamil. Agents that promote heart rate and/or contraction may be used in a preferred embodiment of the present invention. For example, dopamine, a natural catbcliplamine, is known to increase contractility. Positive inotropes are agents that specifically increase the force of contraction of the heart. Glucagon, a naturally occurring hormone, is known to increase heart rate and contractility. Glucagon may be used to reverse the effects of a beta-blocker since its effects bypass the beta receptor. Forskolin is known to increase heart rate and contractility. As mentioned earlier epinephrine and norepiriephrine naturally increase heart rate and contractility. Thyroid hormone, phosphodiesterase inhibitors and prostacyclin, a prostaglandin are also known, to increase heart rate and contractility. In addition, methylxanthines are known to prevent adenosine from interacting with its cell receptors.

[0094]

Typically, vagal nerve stimulation prevents the heart from contracting. This non-contraction must then be followed by periods. Without vagal nerve stimulation during which the heart is allowed to contract, and blood flow is restored throughout the body. At block 517, the state of cerebral blood circulation may be monitored. This monitoring may occur at specific points during the procedure, for example, as shown at block 517. Alternatively, monitoring may occur continuously. If cerebral blood circulation is sufficient, then all or a portion of the medical procedure may be carried out (Block 520). However, if the state of cerebral blood circulation is not sufficient, then a signal may indicate that the state of blood circulation to the brain is insufficient. If the sensor indicates that the state of blood circulation is insufficient, the surgeon may proceed to block 530, where the nerve stimulation is ceased an the heart is allowed to contract. The cardiac stimulator may be used to cause the heart to contract. Alternatively, unit 200 may automatically proceed to Block 530 to cease nerve stimulation. In addition, Unit 200 may automatically begin cardiac stimulation.

[0095]

The state of cerebral blood circulation sensed by sensor 5 may be communicated to the surgeon by a number of suitable means. For example, the ambient blood flow may be indicated on a display or monitor. A visual or audio signal may indicate when the level of cerebral blood flow reaches a certain level, e.g. when blood flow is insufficient. Alternatively, the system of the present invention may “lock” the controls of the vagal stimulator in an “off” state when cerebral blood flow reaches a predetermined condition, thereby indicating that blood flow is insufficient. The system may then release the controls when the state of cerebral blood circulation sensed by the sensor is again sufficient.

[0096]

Additionally, the amount of vagal nerve stimulation used may be adjusted based on the output of the sensor 5. For example, the level of stimulation may be lowered or the duration of stimulation may be lowered if the sensor indicates that cerebral blood circulation at 517 is insufficient. This adjustment may be automatic or may be controlled by the surgeon.

[0097]

At Block 520, a medical procedure may be performed or begun. Such a procedure may be for example surgery on the heart. Alternatively, the procedure may be surgery performed on another organ of the body.

When the medical procedure comprises one or more medical devices, e.g., coated stents, these devices may be coated with one or more radioactive materials and/or biological agents such as, for example, an anticoagulant agent, an antithrombotic agent, a clotting agent, a platelet agent, an anti-inflammatory agent an antibody, an antigen, an immunoglobulin, a defense agent, an enzyme, a hormone, a growth factor, a neurotransmitter, a cytokine, a blood agent, a regulatory agent, a transport agent, a fibrous agent, a protein, a peptide, a proteoglycan, a toxin, an antibiotic agent, an antibacterial agent, an antimicrobial agent, a bacterial agent or component, hyaluronic acid a polysaccharide, a carbohydrate, a fatty acid, a catalyst, a drug, a vitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, an antiviral agent, a viral agent or component, a genetic agent, a ligand and a dye (which acts as a biological ligand). Biological agents may be found in nature (naturally occurring) or may be chemically synthesized.

[0100]

The medical procedure may be non-invasive, minimally invasive and/or invasive. The medical procedure-may entail a port-access approach, a partially or totally endoscopic approach, a sternotomy approach or a thoracotomy approach. The medical procedure may include the use of various mechanical stabilization devices or techniques as well as various robotic or imaging systems.

[0101]

In one method, the heart may be temporarily slowed or intermittently stopped for short periods of time to permit the surgeon to accomplish the required surgical task and yet still allow the heart itself to supply blood circulation to the body. For example, stimulation of the vagus nerve in order to temporarily and intermittently slow or stop the heart is described in U.S. Pat. No. 6,006,134 entitled “Method and Device for Electronically Controlling the Beating of a Heart Using Venous Electrical Stimulation of Nerve Fibers”, Dec. 21, 1999, to Hill and Junkman. This patent is assigned to Medtronic, Inc. and is incorporated herein by reference.

[0102]

During this medical procedure, the state of cerebral blood circulation may be monitored constantly or intermittently as described above. An assessment, for example, of the amount of blood flowing to the brain may again be taken at block 525. If the state of cerebral blood circulation is sufficient the physician may continue with the medical procedure that is in progress. However, if the state of cerebral blood circulation is not sufficient, then the sensor 5 may indicate that blood circulation to the brain is insufficient. If the sensor indicates that blood circulation is insufficient, the surgeon may proceed to Block 530, where the nerve stimulation is ceased. The heart will therefore be allowed to contract and thus blood will again be allowed to flow to the brain and vital organs. The cardiac stimulator maybe used to cause the heart to contract. Alternatively, unit 200 may automatically proceed to Block 530 to cease nerve stimulation. In addition, Unit 200 may automatically begin cardiac stimulation. Additionally the amount of vagal nerve stimulation used may be adjusted based on the output of the sensor 5. For example, the level of stimulation may be lowered or the duration of stimulation may be lowered if the sensor indicates that cerebral blood circulation at 525 is insufficient.

[0103]

After a time, the medical procedure or one phase of the procedure is completed at 520. After some phase of the medical procedure is performed, cardiac contractions are allowed to occur (Block 530). Cardiac contractions may need to occur intermittently during the procedure to ensure adequate blood flow. In one embodiment, the stimulation from the nerve stimulator 10 is stopped or slowed enough to allow the heart to contract. For example, the vagal nerve stimulation is removed, thereby allowing cardiac contractions to occur.

[0104]

In another embodiment, the heart may be stimulated to ensure that cardiac contractions occur (Block 535). For example, cardiac stimulator 20 may be used to apply pacing pulses to the heart to encourage the heart to contract normally. In particular, the pacing pulses may be applied to the ventricle as is well known in the field. Additionally, the amount of cardiac stimulation used may be adjusted based on the output of the sensor 5. For example, the level of stimulation may, be increased or the duration of stimulation may be increased if the sensor indicates that cerebral blood circulation at 525 is insufficient.

[0105]

The present invention permits the heart to be stilled or quiescent for selected and controllable periods of time in order to permit a medical procedure to be performed. While such a period of stillness or quiescence is desired, it must not last too long, otherwise insufficient blood and oxygen is delivered to organs. Thus, it is necessary to have the periods when the heart is beating (Blocks 530, 535).

[0106]

The state of cerebral blood circulation, for example, sensed by sensor 5 while the heart is beating may be communicated to the surgeon by a number of suitable means. For example, ambient blood flow may be indicated on a display or monitor. A visual or audio signal may indicate when the level of cerebral blood flow reaches a certain level, e.g. when blood flow is insufficient. Alternatively, the system of the present invention may “lock” the controls of the cardiac stimulator in an “on” state when the state of cerebral blood circulation reaches a predetermined condition, thereby indicating that blood circulation is insufficient. The system may then release the controls when the state of blood circulation sensed by the sensor is again sufficient.

[0107]

If additional medical procedures or additional stages of medical procedures need to be performed, the heart may again be stilled using the methods of stilling the heart described above. Therefore from Block 530 or Block 535, the method may be repeated (as in the loop designated by 540). For example, the heart may again be prevented from contracting by stimulation of the vagal nerve (510). Additional drugs may be delivered or the drugs previously administered may continue to be administered.

[0108]

This cycle may be repeated until the procedure, such as the surgery, is completed. As the cycle continues sensor 5 enables monitoring of the state of blood circulation and, if necessary, appropriate adjustment of nerve stimulation and cardiac stimulation to ensure sufficient blood circulation.

[0109]

For example, the surgical procedure at 520 may require several stitches to be made by the surgeon. The surgeon may stimulate the vagal nerve, at 510 to stop the heart. Then the surgeon may make the first stitch at 520. The surgeon may then reduce or halt stimulation at 530 and allow the heart to contract. The surgeon may also pace the heart at 535. Then at 540, the surgeon may return to 510 to inhibit contractions of the heart. At 520, the surgeon will then make the second stitch. This process may be repeated (the loop designated by 540 may be repeated) until all the required stitches have been made. Meanwhile, the state of blood circulation is monitored continuously or, for example at Blocks 517 and 525 by sensor 5. The procedure may proceed uninterrupted if the state of blood circulation remains sufficient.

[0110]

If required, after the procedure is completed, step 535 may be performed until the heart is beating normally. Step 545 may be continued until, the physician is satisfied that the heart is beating normally and the state of blood circulation has reached an acceptable level.

[0111]

FIG. 4 is a timeline showing the relationship of a sensor, a nerve stimulator and a cardiac stimulator in one embodiment of the present invention.

[0112]

Point 610 indicates a point before the medical procedure has begun. At this point 610, both nerve stimulation and cardiac stimulation are off. At point 610, the heart is beating regularly. The patients state of cerebral blood circulation, for example, may be measured by sensor 5 at point 610. Thus sensor 5 may be turned on at point 610.

[0113]

Then nerve stimulation is turned on to inhibit beating of the heart. During phase 601, the vagal nerve stimulation is on and the cardiac stimulation is off. This is the condition of the two types of stimulation at step 520 described above. In one embodiment, shown in FIG. 3 sensor 5 is on throughout the entire procedure. Alternatively, sensor 5 may be turned on during phase 601 to check the state of cerebral blood circulation (as described at Block 517).

[0114]

Point 611 is a representative point during phase 601. At point 611 the contractions of the heart are stilled or substantially slowed. Also, at point 611, the current state of cerebral blood-circulation may be determined (as described at Blocks 517 and 525). If the state of cerebral blood circulation at point 611 is sufficient, then the medical procedure can proceed (as described at Block 520). However, if the state of cerebral blood circulation is not sufficient at point 611, sensor 5 may provide a signal indicating that the state of cerebral blood circulation is insufficient. The surgeon may then proceed immediately to phase 602. Alternatively, control unit 200 may automatically proceed to phase 602 after providing the signal.

[0115]

Additionally, the amount of vagal stimulation used may be adjusted based on the output of the sensor 5. For example, the level of stimulation may be decreased or the duration of stimulation may be decreased if the sensor indicates that the state of blood circulation, at point 611 is insufficient.

[0116]

During phase 602 the vagal stimulation is turned off (as described at step 530) and the cardiac stimulation may be turned on (as described at 535). Point 612 is a representative point during phase 602. At point 612, the contractions are allowed and/or may be induced. In one embodiment, sensor 5 is still on during phase 602. Alternatively, sensor 5 may be turned on during phase 602 to check the state of blood circulation to the brain.

[0117]

Additionally, the amount of cardiac stimulation used may be adjusted based on the output of the sensor 5. For example, the level of stimulation may be increased or the duration of stimulation may be increased if the sensor indicates that cerebral blood circulation at point 612 is insufficient.

[0118]

During phase 603, the vagal nerve stimulation is again turned on and the cardiac stimulation is turned off. Also, during phase 603, sensor 5 may still be on. The amount or duration of vagal stimulation during phase 603 may be different than the amount or duration of vagal stimulation during phase 601, based on the data gathered from sensor 5 during phase 601. Alternatively, the current state of cerebral blood circulation may again be determined during phase 603 (as described at Block 525). Point 613 is a representative point during phase 603. If the state of blood circulation at point 613 is sufficient, then the medical procedure can proceed (as described in step 520). However, if the state of blood circulation is not sufficient at point 611, sensor 5 may provide a signal indicating that blood circulation is insufficient. The surgeon may then proceed immediately to phase 602. Alternatively control unit 200 may automatically proceed to phase 602 after providing the signal. Additionally, the amount of vagal stimulation used may again be adjusted based on the output of the sensor 5.

[0119]

During phase 604 the vagal stimulation is again turned off and the cardiac stimulation may again be turned on. The amount or duration of cardiac stimulation during phase 604 may be different than the amount or duration of cardiac stimulation during phase 602, based on the data gathered from sensor 5 during the previous phases.

[0120]

The method of the present invention may be repeated as necessary until a point is reached, represented by point 615, when the necessary medical procedures are completed. At this point 615, nerve stimulation is off although cardiac stimulation may be left on in order to pace the heart to its normal rhythm. At point 615, the state of cerebral blood circulation may be checked for a final time (as described at 545).

[0121]

It will be appreciated by those skilled in the art that while the invention has been described above in connection with particular embodiments and examples, the invention is not necessarily so limited, and that numerous other embodiments examples, uses, modifications and departures from the embodiments, examples and uses are intended to be encompassed by the claims attached hereto.